Epothilone A (R═H) and Epothilone B (R═CH3) are produced by Sorangium cellulosum strain So ce 90, the structures of which are shown below, and were the first of several epothilones to be isolated, synthesized, and characterized. Höfle et al., 1996, Angew. Chem. Int. Ed. Engl. 35(13/14): 1567–1569.

Epothilone A and epothilone B possess many of the advantageous properties of paclitaxel (Taxol®, Bristol-Myers Squibb). As a result, there is significant interest in these and structurally related compounds as potential chemotherapeutic agents. The desoxy counterparts of epothilones A and B are known as epothilone C (R═H) and epothilone D (R═CH3), and exhibit similar anti-tumor activity but with less cytotoxicity. The structures of epothilones C and D are shown below.

Although other naturally occurring epothilones have been described, these compounds are produced in exceedingly small amounts. PCT publication WO 99/65913 describes 39 naturally occurring epothilones obtained from Sorangium cellulosum So ce 90 of which epothilones A, B, C, and D together account for approximately 98.9% of the total epothilones produced. The 35 other naturally occurring epothilone compounds together account for the remaining 1.1% and include epothilone C6 (which may also be referred to as 10,11-dehydroepothilone C) and whose structure is shown below

The naturally occurring epothilones can be modified through semisynthesis. PCT publication WO 99/27890 describes conversion of epothilones A and B into their lactam analogs. PCT publication WO 99/54318 describes conversion of epothilones C and D into their 12,13-cyclopropane analogs.
Additional epothilone analogs may be produced through de novo synthesis. PCT publications WO 99/07692 and WO 00/00485 describe a synthetic route wherein the methyl group at C-6 is replaced by other aliphatic groups and unsaturation may be introduced at the 10,11-position. PCT publication WO 99/02514 describes total synthesis of lactam analogs of epothilones.
Due to the increasing interest in epothilones as anti-cancer agents, novel derivatives of these compounds are needed and desired to more fully develop their therapeutic potential. The present invention fulfils this need.